Vitamin A is commercially prepared by extraction from fish liver oils or by chemical synthesis from the reaction of beta ionone and a propargyl halide. Other syntheses include starting with beta ionone, converting it to beta iononyl, and reacting it with 3-formylcrotonyl acetate to make retinol acetate. Alternatively, beta ionone can be converted to the corresponding aldehyde and through a Grignard reaction with 3 methyl-2-pentene-4-yn-1-ol and a partial hydrogenation and rearrangement converts it to retinol acetate. Retinol acetate is converted to retinol palmitate through a transesterification reaction with methyl palmitate. Both retinol acetate and retinol palmitate are commonly used for supplementation.
The most stable and more bioavailable form of Vitamin A is the trans isomer. The cis isomeric forms, i.e., 13-cis retinol, 9-cis retinol, and 9, 13-di-cis retinol materials are less stable. Cis isomers are formed during production and they oxidize more readily than the trans isomers.
Commercial vitamin A contains a number of impurities which are present either due to oxidation or as left over solvents or by products of the synthesis of vitamin A. One of the key reactants and/or oxidation products of vitamin A is beta ionone. The percentage of beta ionone as well as the level of cis isomers of vitamin A can be used to determine vitamin A quality.
Even when vitamin A palmitate or acetate is prepared and purified, it readily oxidizes creating beta-ionone and other oxidation products. Spray dried vitamin A, that is, vitamin A which is spray dried or partially encapsulated with pectin, starches, gum, or other suitable material, is more stable to oxidation, but it also can contain from 10-30% cis isomers vitamin A and solvents remaining from the synthesis or the transesterification reaction. Even this form of vitamin A can oxidize over time.
Beta ionone which is a key impurity in vitamin A has a cedar wood or raspberry aroma and is used in perfumes. It has a very low threshold level. This is just one of many odors associated with vitamin A oxidation products. Aldehydes and ketones are also formed, particularly hexanal, 5-nonen-2-one, 2-decenal, and octanal. Hydrocarbons such as hexane, cyclopentane, ethyl cyclohexane and nonane can also be present. All of these materials have unpleasant odors and flavors.
Accordingly, it is desirable to have a vitamin A which is substantially free of oxidation products, solvents, and has less than 5% of the cis isomer. Such a vitamin A has been found to be tasteless and odorless. It would also be desirable to stabilize this material against oxidation.
It has now been found that vitamin A can be purified to remove essentially all of the volatile materials boiling below 50.degree. C., and, stabilized to prevent further oxidation. It is therefore an object of this invention to provide a tasteless, odorless, storage-stable vitamin A. It is also an object of this invention to make a vitamin A which contains .beta.-ionone at levels below its threshold value. These and other objects of the invention will be evident from the description following.